Adrenocortical carcinoma (ACC) is a very rare endocrine tumour, with variable prognosis, depending on tumour stage and time of diagnosis. The overall survival is five years from detection. Radical surgery is considered the therapy of choice in the first stages of ACC. However postoperative disease-free survival at 5 years is only around 30% and recurrence rates are frequent. o,p’DDD (ortho-, para’-, dichloro-, diphenyl-, dichloroethane, or mitotane), an adrenolytic drug with significant toxicity and unpredictable therapeutic response, is used in the treatment of ACC. Unfortunately, treatment for this aggressive cancer is still ineffective. Over the past years, the growing interest in ACC has contributed to the development of therapeutic strategies in order to contrast the neoplastic spread. In this paper we discuss the most promising therapies which can be used in this endocrine neoplasia. 1. Introduction Adrenocortical carcinoma (ACC) is a rare malignant disease with poor prognosis and an estimated incidence between 1 and 2 per million population annually [1–4]. The age distribution is reported as bimodal with a first peak in childhood and a second higher peak in the fourth and fifth decade [3, 4]. Genetic studies performed on ACC were focused on molecular alterations either at the germline level in rare familial diseases or at somatic level in sporadic tumors. These advances underline the importance of genetic alterations in ACC development and indicate various chromosomal regions (2, 11p15, 11q, 17p13) and genes (IGF-II, p53, β-catenin, etc.), potentially involved in ACC [5–11]. In particular, the monoclonality analysis indicates that tumor progression is the final result of an intrinsic genetic mutation, whereas polyclonality suggests that tumor cells are affected by local or systemic stimuli. Analysis of the pattern of X-chromosome inactivation in heterozygous female tissue shows that ACC consists of monoclonal populations of cells [12]. Molecular alterations lead to inactivation of the tumor suppressor genes and sequential activation of the oncogenes. The insulin growth factor II (IGF-II) system, located at 11p15, is heavily involved in ACC ethiopathogenesis [5]. Loss of heterozygosity (LOH) at chromosome region 11p15, associated with a higher risk of tumor recurrence, is more frequent in ACC than in adrenal adenomas [6]. The development of ACC may be due to an activation of the Wnt signaling pathway caused by germline mutations of the Adenomatous Polyposis Coli (APC) gene [7, 8]. Germline mutations in TP53 are identified in 70% of families with
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